Thursday, November 2, 2017

Estimation of Direct Medical Costs Related to Chronic Hepatitis C: A Rationale for Early Antiviral Therapy

Gut and Liver 2017; 11(6): 745-746

Estimation of Direct Medical Costs Related to Chronic Hepatitis C: A Rationale for Early Antiviral Therapy
Do Young Kim Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

See “Healthcare Costs for Chronic Hepatitis C in South Korea from 2009 to 2013: An Analysis of the National Health Insurance Claims’ Data” by Moran Ki, et al. on page 835, Vol. 11. No. 6, 2017

In medicine, cost-of-illness studies play a role as they might be used as references for resource allocation, development of policy, and for determination of the cost-effectiveness of new therapies.1 Chronic hepatitis C (CHC) is a serious worldwide health-related burden, and recent development and introduction of direct-acting antivirals (DAAs) for CHC has made a substantial push toward looking the disease from the economic point of view.2 Economic impact of CHC and its management can be evaluated by two different approaches. The first is cost-of illness study, where only immediate costs of treatment for CHC are considered. Whereas, cost-effectiveness study usually needs more assumptions and should include clinical outcomes such as disease related morbidity or mortality. Thus, cost-of-illness studies may provide actual and fundamental data to properly conduct cost-effectiveness studies.

Various methodologies in the area of health economy can be applied to cost-of-illness studies, each having its own advantages and disadvantages. Furthermore, because of divergence in healthcare system and reimbursement policy, it is almost impossible to compare directly the costs incurred by a disease among countries. It is also noteworthy that many of the studies estimate only direct costs related to the disease, excluding indirect costs such as loss of productive job and transportation fees due to absent or incorrect data.3

Cost-estimation studies related to CHC have not been presented in Asian region, even though such countries as Japan and Taiwan have a high prevalence of hepatitis C virus (HCV) infection. In this regard, the article by Ki et al .4 in this issue might be relevant, which examined the annual per-patient costs for CHC, cirrhosis and hepatocellular carcinoma (HCC) using Korean public data. The National Health Insurance (NHI) and Health Insurance Review and Assessment (HIRA) claim data between 2009 and 2013 were the sources for the investigation. Indeed, the NHI in South Korea is an unique healthcare system, where both costs incurred by inpatient and outpatient care are co-paid by government and patient himself, leaving some items such as practices, drugs and devices still nonreimbursed. The merit of including all the people in Korean national insurance system pushed the ex-president of the U.S., Mr. Obama, to revolve U.S. healthcare system and to make “Patient Protection and Affordable Care Act,” the so called “Obama Care.” In real practice, however, Korean NHI system has produced lots of abnormal and deviated medical practices due to limited resources, budget and non-optimal insurance costs given to the physicians. Anyhow, the national universal insurance system enabled the authors to perform a comprehensive and uniform cost-of-illness study regarding HCV infection, encompassing all the disease states from hepatitis to HCC, and all the classes of hospitals from private clinic to tertiary university hospital.

In the article of Ki et al .,4 a total of 181,768 patients were identified during the study period, and the direct annual per patient medical costs, which were calculated by prevalence based approach, increased from CHC to cirrhosis, HCC and the first year post-liver transplantation; 895, 1,873, 6,945, and 67,359 USD, respectively. As expected, the direct medical costs increased with progression of CHC, because complications of cirrhosis such as ascites, variceal bleeding or HCC required hospitalization and resource utilization. Increasing direct medical costs per patient with more advanced CHC-related disease were also shown in a previous Korean study, where cost data on 445 CHC patients from eight institutions were retrospectively reviewed and the monthly direct costs per patient in CHC, compensated cirrhosis and HCC were estimated to be 77, 98, and 504 USD, respectively.5 Thus, annual costs per patient in each disease state are calculated to be 924, 1,176, and 6,048 USD, respectively, which are similar to the estimates in Ki’s study.

The number of patients who received antiviral therapy with interferon (or pegylated interferon) and/or ribavirin at least once was 25,223 accounting for 13.9% of all the patients between 2009 and 2013. Interestingly, the costs per patient during the study period were 19,743 USD in those who underwent antiviral therapy, while the costs in those who did not undergo antiviral therapy were 3,126 USD. A substantial proportion (78.5%) of costs in patients who received antiviral therapy was incurred by drugs including pegylated interferon. However, 37.2% of the total costs were incurred by drugs other than antiviral agents in those who did not undergo antiviral therapy. What should be kept in mind is that cost-of-illness study just estimates immediate costs, and it might be addressed by another kind of cost study whether antiviral treatment-related high costs could lower overall costs in long-term outcomes.

The authors in their study highlighted low rates of anti-HCV treatment uptake (13.9%) over 5-year period. Though these figures might underestimate the real rates of treatment because some patients had already underwent antiviral therapy before the study period, indeed a significant proportion of CHC patients did not received therapy in the interferon era due to various reasons including advanced liver fibrosis, old age and fear of adverse events. Additional finding related to antiviral therapy is that 1,471 patients received ribavirin monotherapy without interferon or pegylated interferon, which is not a recommended regimen. There is a need of advertisement and education on the proper anti-HCV regimen for physicians in the community utilizing this analysis.

Claim data have its own limitations, resulting in inaccuracy and ambiguity. As the authors stated, it may be argued whether diagnosis of CHC, cirrhosis and HCC was accurately made with ICD-10 codes. Unfortunately, the costs related to management of decompensated cirrhosis were not separately estimated due to this limitation. Exclusion of non-reimbursed costs from the estimation, and the possibility of including costs incurred by comorbidities not by CHC itself are also disadvantages.

It has been apparent that healthcare costs increase if CHC related diseases are not properly controlled. Overall, the increase of costs per person for HCC seems to be greater compared to CHC or cirrhosis; from 5,838 to 6,945 USD in HCC versus from 1,470 to 1,873 USD in cirrhosis versus from 813 to 895 USD in CHC (from 2009 to 2013). Therefore, the issue of whether stopping progression of disease with DAAs could decrease healthcare costs needs to be further studied using these data.

No potential conflict of interest relevant to this article was reported.

1. El Khoury AC, Wallace C, Klimack WK, Razavi H. Economic burden of hepatitis C-associated diseases: Europe, Asia Pacific, and the Americas. J Med Econ 2012;15:887-896. 2. Jeong SH, Jang ES, Choi HY, Kim KA, Chung W, Ki M. Current status of hepatitis C virus infection and countermeasures in South Korea. Epidemiol Health 2017;39:e2017017. 3. Rein DB, Borton J, Liffmann DK, Wittenborn JS. The burden of hepatitis C to the United States Medicare system in 2009: descriptive and economic characteristics. Hepatology 2016;63:11351144. 4. Ki M, Choi HY, Kim KA, Jang ES, Jeong SH. Healthcare costs for chronic hepatitis C in South Korea from 2009 to 2013: an analysis of the National Health Insurance claims’ data. Gut Liver 2017;11:835-842. 5. Kim DY, Yoon KT, Kim W, et al. Estimation of direct medical cost related to the management of chronic hepatitis C and its complications in South Korea. Medicine (Baltimore) 2016;95:e3896.

Wednesday, November 1, 2017

Challenges in Treating Genotype 3 Hepatitis C Virus

Challenges in Treating Genotype 3 Hepatitis C Virus
Sustained virological response (SVR), defined as "an HCV RNA level below the threshold of quantification,"4 sustained for 12 to 24 weeks after treatment ends, is considered predictive of cure. In clinical trials of the DAA agent sofosbuvir plus ribavirin, only 30% to 60% of patients with GT3 had SVR after 12 to 16 weeks of therapy compared with 95% of patients with GT2.2,3 Data have shown patients with GT3 HCV have faster progression of fibrosis and higher rates of cirrhosis, severe steatosis, and hepatocellular carcinoma.2,4 Steatosis is associated with higher viral loads, and cirrhosis predicts a lower likelihood of cure in treatment-naive patients, which may help explain the worse SVR rates in patients with GT3 relative to other HCV genotypes.4 Indeed, when SVR in patients with GT3 is stratified according to the presence of compensated cirrhosis or prior treatment failure, previously untreated patients and patients without cirrhosis are much more likely to achieve SVR with DAA therapy...

Comment - Funding the elimination of viral hepatitis: donors needed

The Lancet Gastroenterology & Hepatology
Funding the elimination of viral hepatitis: donors needed
Charles Gore , Jessica Hicks, Wouter Deelder
Published: 31 October 2017


PDF Download

Chronic hepatitis B and C are life-threatening infectious diseases that cause serious liver damage, cancer, and premature death. More than 300 million people are infected with hepatitis B or hepatitis C1 and are at risk of developing escalating health problems. These infectious diseases cause 1·3 million deaths every year1 and are responsible for more than half of all new cases of liver cancer and one in every 12 cancer deaths.2 Whereas the burden of other major infectious diseases such as HIV, tuberculosis, and malaria is decreasing as a result of consistent large-scale global investment, viral hepatitis has been neglected, resulting in ever increasing numbers of people dying from hepatitis B and C...

Liver transplantation for HCV in the United States 2002–2014: An analysis of the UNOS/OPTN registry

Liver transplantation for chronic hepatitis C virus infection in the United States 2002–2014: An analysis of the UNOS/OPTN registry
Georg Dultz, Barry I. Graubard, Paul Martin, Martin-Walter Welker, Johannes Vermehren, Stefan Zeuzem, Katherine A. McGlynn , Tania M. Welzel
Published: October 31, 2017

View Online
Download PDF

Chronic hepatitis C virus (HCV) infection is a leading cause for orthotopic liver transplantation (OLT) in the U.S. We investigated characteristics of HCV-infected patients registered for OLT, and explored factors associated with mortality. Data were obtained from the United Network for Organ Sharing and Organ Procurement and Transplantation network (UNOS/OPTN) registry. Analyses included 41,157 HCV-mono-infected patients ≥18 years of age listed for cadaveric OLT between February 2002 and June 2014. Characteristics associated with pre- and post-transplant survival and time trends over the study period were determined by logistic and Cox proportional hazard regression analyses and Poisson regressions. Most patients were white (69.1%) and male (70.8%). At waitlist registration, mean age was 54.6 years and mean MELD was 16. HCC was recorded in 26.9% of the records. A total of 51.2% of the patients received an OLT, 21.0% died or were too sick; 15.6% were delisted and 10.4% were still waiting. Factors associated with increased waitlist mortality were older age, female gender, blood type 0, diabetes, no HCC and transplant region (p<0.001). OLT recipient characteristics associated with increased risk for post OLT mortality were female gender, age, diabetes, race (p<0,0001), and allocation MELD (p = 0.005). Donor characteristics associated with waitlist mortality included age, ethnicity (p<0.0001) and diabetes (p<0.03). Waitlist registrations and OLTs for HCC significantly increased from 14.4% to 37.3% and 27.8% to 38.5%, respectively (p<0.0001). Pre- and post-transplant survival depended on a variety of patient-, donor-, and allocation- characteristics of which most remain relevant in the DAA-era. Still, intensified HCV screening strategies and timely and effective treatment of HCV are highly relevant to reduce the burden of HCV-related OLTs in the U.S.

NC Medicaid Program Removes Hepatitis C Treatment Restrictions

NC Medicaid Program Removes Hepatitis C Treatment Restrictions

8 things to know ahead of the World Hepatitis Summit

8 things to know ahead of the World Hepatitis Summit

Devex spoke with Hirnschall and Marc Bulterys, team leader of the Global Hepatitis Program at the WHO in Geneva, about the gaps, outstanding challenges, and ongoing work toward elimination. Here’s what you can expect from the three-day meeting.

Relationship between obesity, nonalcoholic steatohepatitis cirrhosis and a rising liver transplant burden

NASH May Overtake Hepatitis C as Top Liver Transplant Cause
Shantell M. Kirkendoll
A Michigan Medicine researcher outlines the relationship between obesity, nonalcoholic steatohepatitis cirrhosis and a rising liver transplant burden.

Obesity is driving the rise of nonalcoholic steatohepatitis cirrhosis (NASH), the end of the fatty liver disease spectrum that begins with accumulation of fat in the liver, followed by ballooning, scarring, cirrhosis and eventually liver failure and cancer.

There are no drugs to treat fatty liver disease, which is quickly becoming a leading cause of liver transplants.

Neehar Parikh, M.D., M.S., a liver specialist and clinical lecturer at Michigan Medicine, is examining the pace at which America’s obesity rate is putting pressure on the transplant community.

Read more:

Nine countries now on track to eliminate hepatitis C

Global progress towards hepatitis C elimination still blocked by cost of treatment, lack of diagnosis
Keith Alcorn
Published: 01 November 2017
According to the Polaris Observatory estimates just over half of people with hepatitis C in the United States are aware of their infection. Although rates of diagnosis are high in New York state (81%) and California (71%), other states are doing less well, and the United States is also experiencing a sharp increase in new hepatitis C infections in young adults and adolescents as a result of sharing of injecting equipment.

Nine countries now on track to eliminate hepatitis C
1 Nov 2017 Tara Farrell

[Sao Paulo, 1 November 2017] New data on hepatitis C released by the Polaris Observatory* and presented today at the World Hepatitis Summit (WHS) in Sao Paulo, Brazil show that nine countries — Australia, Brazil, Egypt, Georgia, Germany, Iceland, Japan, the Netherlands and Qatar — are on course to eliminate hepatitis C by 2030.

Worldwide, viral hepatitis kills more than one million people each year, and more than 300 million people are chronically infected with hepatitis B or C. Yet, with the development of highly-effective direct acting antivirals (DAAs) for hepatitis C and the increasing rates of hepatitis B treatment and vaccination coverage globally, elimination of viral hepatitis has become a real possibility.

“This new data shows that elimination of hepatitis C is possible but it also shows more must be done to support governments in tackling viral hepatitis,” said Charles Gore, President of the World Hepatitis Alliance. “The World Hepatitis Summit offers governments the opportunity to learn from other countries and public health experts, in an effort to speed up progress to elimination.”

Since the adoption of World Health Organization’s (WHO) elimination targets in 2016, which include a 90% reduction of new hepatitis B and C infections and a 65% reduction in hepatitis B and C related mortality by 2030, some countries are making great strides yet multiple factors preventing progress remain for the majority. These include a lack of political will and global funding mechanisms, poor data and surveillance, access to diagnostics and medicines and poor diagnosis rates (approx. 10% worldwide for hepatitis B and 20% for hepatitis C), that together mean that many countries are struggling to reach the targets.

Some key countries which are being highlighted at the Summit for their innovative work to eliminate viral hepatitis are Brazil, Egypt, Australia and Georgia. In 2017, Egypt pledged to test 30 million for hepatitis C by the end of 2018 by implementing mass screening initiatives (including assistance from the military), as well as mass producing generic copies of DAA drugs for under US $200 per 12-week course.

Meanwhile, WHS host nation Brazil has committed to gradually lift treatment restrictions in 2018, meaning that the country will be able to treat all people infected with hepatitis C, ensuring it is on target to eliminate hepatitis C. Previously, treatment was restricted to only the sickest patients with advanced liver disease.

“Brazil has championed the cause of hepatitis on the world stage for many years and has pushed for an intensified global hepatitis response,” says Adele Schwartz Benzaken, director of the Brazilian Ministry of Health’s Department of Surveillance, Prevention and Control of STIs, HIV/AIDS and Viral Hepatitis. “In addition to the work we have already done on hepatitis B, opening up vaccination to the whole population, we are now gradually removing the restrictions on access to hepatitis C treatment – so that, from 2018 on, the entire infected population can be treated, not just the sickest.”

The Australian government responded to the call for universal access to the hepatitis C DAAs with an AUS $1billion dollar investment over 5 years. This risk-sharing agreement with pharmaceutical companies provides government-funded treatment to all adults without restriction and has paved the way for the elimination of hepatitis C by 2030. More than 30,000 patients with hepatitis C were treated and cured in 2016.

“What we are seeing is that some countries, especially those with a high burden, are making the elimination of viral hepatitis a priority and are looking at innovative ways to do it,” said Home Razavi, Director of CDA. “However, it will be near-impossible for most other countries to meet the WHO targets without a huge scale-up in political will and access to diagnostics and treatment.”

Although only a handful of countries are currently on track to reach the WHO’s elimination targets, there are a number of other countries which are making progress. Mongolia, Gambia, and Bangladesh have shown real political will and, along with Brazil, Georgia and Egypt, are spearheading the NOhep Visionary Programme** in their region, due to their commitment to ending their epidemics.

“Because viral hepatitis has been neglected for so long, much needs to be done rapidly to make up for lost time,” concluded Gore. “In that context, the Summit, a biennial event, focuses on the public health approach to viral hepatitis and acts as the central forum for countries to share their experience and best practice in order to drive rapid advances in national responses.”